Risk of Cardiovascular Diseases Among Older Breast Cancer Survivors in the United States: A Matched Cohort Study

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  • 1 Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom;
  • 2 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
  • 3 Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and
  • 4 Royal Marsden Hospital,
  • 5 National Heart and Lung Institute, Imperial College London, and
  • 6 Royal Brompton Hospital, London, United Kingdom.
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Background: It has been suggested that cardiovascular risks are increased in breast cancer survivors, but few studies have quantified the risks of a range of specific clinically important cardiovascular outcomes in detail. Patients and Methods: Women aged >65 years with incident breast cancer from 2004 to 2013 in the SEER-Medicare linked database were matched with 5 cancer-free female counterparts (5:1 ratio). Prevalence of specific cardiovascular outcomes at baseline was measured, then Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of individual cardiovascular outcomes during follow-up. Modification of the effect was investigated by time since diagnosis, race/ethnicity, prior cardiovascular disease (CVD), and age. Results: In all, 91,473 women with breast cancer and 454,197 without breast cancer were included. Women with breast cancer had lower baseline prevalence of all CVDs. Compared with cancer-free controls, breast cancer survivors had substantially increased risks of deep vein thrombosis (adjusted HR, 1.67; 95% CI, 1.62–1.73; 386,484 person-years of follow-up) and pericarditis (HR, 1.43; 95% CI, 1.38–1.49; 390,776 person-years of follow-up); evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease (adjusted HRs ranging from 1.05–1.09, lower CI limits all ≥1); and evidence of lower risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke (adjusted HRs ranging from 0.89–0.98, upper CI limits all ≤1). Increased risks of arrhythmia, heart failure, pericarditis, and deep vein thrombosis persisted >5 years after cancer diagnosis. Conclusions: Women with a history of breast cancer were at increased risk of several CVDs, persisting into survivorship. Monitoring and managing cardiovascular risk throughout the long-term follow-up of women diagnosed with breast cancer should be a priority.

Submitted January 15, 2020; accepted for publication July 24, 2020. Published online January 5, 2021

Author contributions: Study design: Matthews, Bhaskaran, Lund. Data extraction: Matthews, Hinton. Data analysis: Matthews. Manuscript preparation–first draft: Matthews. Critical revision and final approval: All authors.

Disclosures: Dr. Stanway has disclosed that she receives consulting fees from Roche, Clinigen, Eli Lilly, and Novartis. Dr. Lyon has disclosed that he receives consulting fees from Servier, Novartis, Pfizer, Roche, Ferring Pharmaceuticals, Clinigen Group, Boehringer Ingelheim, Amgen, Eli Lily, and Bristol-Myers Squibb. Dr. Smeeth has disclosed that he has received grant/research support from Wellcome, and grant/research support and consulting fees from GlaxoSmithKline. Dr. Bhaskaran has disclosed that he has received grant/research support from Wellcome Trust and the Royal Society. Dr. Lund has disclosed that her spouse is employed by GlaxoSmithKline. The remaining authors have disclosed that they have financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (107731/Z/15/Z) held by Dr. Bhaskaran.

The database infrastructure used for this project was supported through the University of North Carolina Clinical and Translational Science Award (UL1TR001111) and the UNC Lineberger Comprehensive Cancer Center, University Cancer Research Fund via the State of North Carolina. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; NCI’s SEER Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the CDC's National Program of Cancer Registries, under agreement U58DP003862-01 awarded to the California Department of Public Health.

Disclaimers: The ideas and opinions expressed herein are those of the author(s), and endorsement by the State of California Department of Public Health, NCI, and CDC or their Contractors and Subcontractors is not intended nor should be inferred. The interpretation and reporting of data from the linked SEER-Medicare database are the sole responsibility of the authors. Funders of this study had no role in the study design, data analysis, or writing of this report.

Correspondence: Anthony A. Matthews, PhD, Unit of Epidemiology, Karolinska Institutet, Nobels väg 13, 171 65 Solna, Sweden. Email: anthony.matthews@ki.se

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